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Eicosanoids are 20-carbon fatty acids (eicosa- means 20) found in many tissues of the body. These compounds are extremely important in multiple physiologic responses, such as gastric mucosal protection and controlling resistance in various vascular beds. They are also significant mediators of pain and inflammation. Thus, both eicosanoid agonists and antagonists are important, but the antagonists are more commonly used clinically.

Inflammation and pain are common manifestations in rheumatic diseases, and eicosanoid antagonists are heavily prescribed to reduce symptoms. Other drugs modify the cellular- and humoral-immune responses in some autoimmune-mediated rheumatic diseases. These drugs are classified as disease-modifying antirheumatic drugs (DMARDs).

Gout is a disease that results from crystallization of a nucleic acid metabolite—uric acid, in the body. In the joints, this crystallization results in inflammation and pain. Patients with gout are treated with anti-inflammatory drugs, and drugs that either decrease formation of these metabolites or increase their excretion. Drug classes discussed in this chapter are reviewed in Figure 34–1.

Figure 34–1.

Drug classes used in the treatment of inflammation and associated pain. Anti-inflammatory drugs are divided into nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs). The NSAIDs are further divided based on their mechanism of action. Acetaminophen is in a drug class alone because of its mechanism of action. The drugs used in the treatment of gout are classified as acute or chronic therapies. In the acute phase, NSAIDs and glucocorticoids are used to decrease inflammation and associated pain. In the chronic phase, drugs are classified based on whether they inhibit inflammatory cell function (colchicine), increase the excretion of uric acid (uricosurics), or inhibit the formation of uric acid (allopurinol).

The eicosanoids are an important group of endogenous fatty acid derivatives that are produced from arachidonic acid, a normal constituent of cell membranes.


Eicosanoids are synthesized in response to a variety of stimuli (e.g., physical injury, immune reactions). These stimuli activate phospholipases in the cell membrane or cytoplasm, and arachidonic acid is released from membrane phospholipids (Figure 34–2). Arachidonic acid is then metabolized by one of several mechanisms. Metabolism to straight-chain products is performed by lipoxygenase (LOX), ultimately producing leukotrienes (LTs). Alternatively, cyclization by the enzyme cyclooxygenase (COX) results in the production of three major subgroups: prostacyclin (PGI), prostaglandins (PGs), and thromboxane (TX). There are several series for most of the principal cyclized subgroups based on different substituents (indicated by letters A, B, etc.) and different numbers of double bonds (indicated by a subscript number) in the molecule.

Figure 34–2.

Scheme for mediators of inflammation derived from arachidonic acid via the cyclooxygenase (COX) or lipoxygenase pathways. Inhibitory sites of action are presented with dashed arrows. Aspirin and the ...

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